Dataset Information

GRK5 Polymorphisms and Postoperative Atrial Fibrillation following Coronary Artery Bypass Graft Surgery.

ABSTRACT: Postoperative atrial fibrillation (POAF) is a serious yet common complication after coronary artery bypass grafting (CABG) surgery. Previous study have identified multiple genetic susceptibility loci for POAF susceptibility after CABG, although some studies are under-powered. However, none of these studies have been conducted among Asians. In current study, we aim to systematically evaluated the previous positive findings for POAF susceptibility after CABG among Chinese population, using a large population-based, two-stage, case-cohort study. From a discovery cohort of 1,348 patients, a total of nine independent loci were evaluated. Six significant SNPs were then assessed in a separately collected validation cohort of 2,000 patients. After adjustment for clinical predictors of POAF, two variants in GRK5 gene (rs4752292, and rs11198893) were replicated with significance were replicated in the validation cohort. The ORs for each additional copy of minor allele were 1.32 (95% CI: 1.15-1.50, P = 5.82 × 10(-5)) and 1.47 (95% CI: 1.28-1.69, P = 1.16 × 10(-7)), respectively. In this two-stage independently collected cardiac surgery cohorts, genetic variations in the GRK5 gene are independently associated with POAF risk in patients who undergo CABG surgery in Asians.

SUBMITTER: Liu L

PROVIDER: S-EPMC4522662 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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GRK5 Polymorphisms and Postoperative Atrial Fibrillation following Coronary Artery Bypass Graft Surgery.

Liu Lu L Zhang Lijun L Liu Minjie M Zhang Yanqun Y Han Xia X Zhang Zhiqiang Z

Scientific reports 20150803

Postoperative atrial fibrillation (POAF) is a serious yet common complication after coronary artery bypass grafting (CABG) surgery. Previous study have identified multiple genetic susceptibility loci for POAF susceptibility after CABG, although some studies are under-powered. However, none of these studies have been conducted among Asians. In current study, we aim to systematically evaluated the previous positive findings for POAF susceptibility after CABG among Chinese population, using a large ...[more]

PMID: 26235218

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Project description:ImportanceNew-onset postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass graft (CABG) surgery. However, the long-term risk of thromboembolism in patients who develop POAF after CABG surgery remains unknown. In addition, information on stroke prophylaxis in this setting is lacking.ObjectiveTo examine stroke prophylaxis and the long-term risk of thromboembolism in patients with new-onset POAF after first-time isolated CABG surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation (NVAF).Design, setting, and participantsThis cohort study used data from a clinical cardiac surgery database and Danish nationwide registries to identify patients undergoing first-time isolated CABG surgery who developed new-onset POAF from January 1, 2000, through June 30, 2015. These patients were matched by age, sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF in a 1 to 4 ratio. Data analysis was completed from February 2017 to January 2018.Main outcomes and measuresThe proportion of patients initiating oral anticoagulation therapy within 30 days and the rates of thromboembolism.ResultsA total of 2108 patients who developed POAF after CABG surgery were matched with 8432 patients with NVAF. In the full population of 10 540 patients, the median (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7 events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55-0.81; P < .001). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in both patients with POAF (adjusted HR, 0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68; P < .001) compared with patients who did not receive any anticoagulation therapy. Further, the risk of thromboembolism was not significantly higher in patients with POAF compared with those who did not develop POAF after CABG surgery (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24).Conclusions and relevanceNew-onset POAF in patients who had undergone CABG surgery was associated with a lower long-term thromboembolic risk than that of patients who had NVAF. These data do not support the notion that new-onset POAF should be regarded as equivalent to primary NVAF in terms of long-term thromboembolic risk.

Project description:Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to β-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate<0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate<0.25. The most significant probe corresponded to vesicular overexpressed in cancer - prosurvival protein 1 gene (VOPP1; 1.83 fold change; P=3.47×10(-7)), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P=1.54×10(-5)), was down-regulated in patients with postoperative AF. GSEA highlighted the role of VOPP1 in pathways with biologic relevance to myocardial homeostasis, and oxidative stress and redox modulation. Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. In patients undergoing CABG surgery, RAA gene expression profiling, and pathway and eQTL analysis suggested that VOPP1 plays a novel etiological role in postoperative AF despite perioperative BB therapy.

Dataset Information

GRK5 Polymorphisms and Postoperative Atrial Fibrillation following Coronary Artery Bypass Graft Surgery.

Publications

GRK5 Polymorphisms and Postoperative Atrial Fibrillation following Coronary Artery Bypass Graft Surgery.

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